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In mice studies, the SymphNode device was shown to drive tumors into remission, eliminate metastasis, and prevent the growth of new tumors.

January 10, 2023

4 Min Read
The SymphNode device (left), contains nanoparticles (red dots) that release a drug that blocks the activity of regulatory T cells (green), which suppress the body’s response to solid tumors. At the same time, the SymphNode’s microparticles (black dots) attract and beef up cancer-fighting T cells.Image courtesy of Negin Majedi/Symphony Biosciences

A tiny biodegradable sponge about the size of a pencil eraser that is made from alginate, the same jiggly polymer used to thicken pudding, has been shown to drive tumors into remission, eliminate metastasis, prevent the growth of new tumors, and result in longer survival in mice studies. The breakthrough developed by an interdisciplinary UCLA research team is described in a paper published in Nature Biomedical Engineering.

The device, called a SymphNode, works by keeping in check extra white blood cells, known as regulatory T cells, or Treg cells, that surround the tumor. Treg cells protect the tumor but they also play a critical role in safeguarding healthy tissues. Attempting to treat cancer by deactivating Treg cells can have serious consequences throughout the body by causing auto-immune conditions. The approach pioneered by UCLA researchers in laboratory tests uses the SymphNode to target only those Treg cells around the tumor while summoning and strengthening tumor-fighting cells, writes Wayne Lewis on the UCLA Newsroom site. The result has been transformative, according to the paper’s co–corresponding author Manish Butte, UCLA’s E. Richard Stiehm Professor of Pediatric Allergy, Immunology, and Rheumatology and a member of the California NanoSystems Institute at UCLA. “Every solid tumor is crammed with these cells, and they’re why 91% of cancer deaths occur from solid tumors. They’re probably limiting our ability to cure the cancer in the first place.”

When surgically implanted directly next to a tumor, SymphNode stimulates the body’s immune response against cancer in multiple ways, according to the researchers. It slowly releases a drug that blocks the regulatory T cells in the tumor. At the same time, it attracts and beefs up the T cells that kill tumors. The material that the device is made of resembles a lymph node, a welcoming setting for cancer-fighting cells, and has pores lined with antibodies that further activate those cells.

The researchers tested SymphNode in mouse models of both breast cancer and melanoma.

With breast cancer, the device shrank tumors in 80% of mice and prevented the spread of cancer in 100% of them. In the untreated control group of mice, the cancer metastasized to the brains and lymph nodes and killed all of them within a few weeks. The researchers also found that placing a SymphNode next to one breast cancer tumor halted the growth of a second, simultaneous tumor at a different location in the body.

In melanoma, the device shrank tumors in 100% of treated mice, with tumors decreasing to undetectable levels in more than 40% of cases.

In both types of cancer, the treatment significantly extended the life span of mice, in many cases by more than twice that of untreated mice.

Even more promising, mice with breast cancer that were treated with the SymphNode and survived also resisted the growth of a second tumor injected 100 days after the first, indicating that the technology may decrease the risk of cancer returning. Butte, who is also a member of UCLA’s Jonsson Comprehensive Cancer Center, said this resulted from the activity of memory T cells — immune cells “trained” by fighting the original tumor to quickly recognize and combat the same cancer if it comes back at a later time. He added that he believes there are few, if any, cancer therapies currently on the market that seem to similarly enhance memory T cells and keep tumors from coming back.

The team aims to make SymphNode available to treat human cancers in the future by licensing the technology to Symphony Biosciences, a company based at the California NanoSystems Institute’s Magnify startup incubator on the UCLA campus. UCLA alumna Negin Majedi, Symphony’s co-founder and CEO, and Mahdi Hasani, the company’s chief scientific officer and a UCLA project scientist, are inventors of the SymphNode and co–first authors of the current research.

Symphony is currently developing a smaller, injectable version of the SymphNode, which the team envisions as a potential addition to chemotherapy or other first-step cancer treatments. The company hopes to initially apply the technology to triple-negative breast cancer, an aggressive form of the disease that lacks targeted therapies. Majedi estimates clinical trials could launch sometime in 2024.

The type of interdisciplinary research needed to create the SymphNode could only happen at a place like UCLA, according to Hasani.

“We have a medical school close to an engineering school,” he said. “In the middle, we have the CNSI, with its core facilities and an incubator space for startup companies. With a setup like that, we can bring together the best of many worlds.”

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